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PDBsum entry 2d51
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References listed in PDB file
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Key reference
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Title
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Structural insight into chain-Length control and product specificity of pentaketide chromone synthase from aloe arborescens.
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Authors
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H.Morita,
S.Kondo,
S.Oguro,
H.Noguchi,
S.Sugio,
I.Abe,
T.Kohno.
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Ref.
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Chem Biol, 2007,
14,
359-369.
[DOI no: ]
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PubMed id
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Abstract
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The crystal structures of a wild-type and a mutant PCS, a novel plant type III
polyketide synthase from a medicinal plant, Aloe arborescens, were solved at 1.6
A resolution. The crystal structures revealed that the pentaketide-producing
wild-type and the octaketide-producing M207G mutant shared almost the same
overall folding, and that the large-to-small substitution dramatically increases
the volume of the polyketide-elongation tunnel by opening a gate to two hidden
pockets behind the active site of the enzyme. The chemically inert active site
residue 207 thus controls the number of condensations of malonyl-CoA, solely
depending on the steric bulk of the side chain. These findings not only provided
insight into the polyketide formation reaction, but they also suggested
strategies for the engineered biosynthesis of polyketides.
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Figure 3.
Figure 3. Overall Structure of PCS Complexed with CoA-SH
(A) Ribbon representation of the PCS homodimer. The monomers are
colored green and silver, and the CoA-SH molecules are shown as
blue stick models. The catalytic Cys174 and Met147, which form a
partial wall of the active-site cavity of another monomer, are
highlighted as yellow CPK and stick models, respectively.
(B) Comparison of PCS (green), M. sativa CHS (blue), and G.
hybrida 2PS (purple). The catalytic Cys174 and the bound CoA-SH
in PCS are also shown as yellow and red CPK molecules,
respectively.
(C) CoA-SH binding to the PCS structure. The
CoA-SH (green) and the SIGMA-weighted |2F[o] − F[c]| electron
density (0.8σ, red cage) for CoA-SH are shown. The water
molecules (light-blue spheres) and hydrogen bonds (dotted lines)
are also indicated.
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Figure 6.
Figure 6. Schematic Representation of the Active-Site
Architecture of Wild-Type PCS, the M207G Mutant, and M. sativa
CHS
(A–C) The M207G substitution opens a gate to the
buried pocket A that extends into the “floor” of the
active-site cavity, resulting in a 4:1 mixture of SEK4b:SEK4
instead of 5,7-dihydroxy- 2-methylchormone. PCS locks the methyl
end of its linear pentaketide intermediate between Met207 and
Val351, as in the case in which M. sativa CHS locks the aromatic
ring derived from 4-coumaroyl-CoA with the coumaroyl-binding
pocket.
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The above figures are
reprinted
by permission from Cell Press:
Chem Biol
(2007,
14,
359-369)
copyright 2007.
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